SUMMARY/ABSTRACT Human infections with Borrelia burgdorferi (Bb) the causative agent of Lyme disease, and other tick-borne pathogens are major and emerging health threats in the United States. The geographic range of tick vectors is expanding within the US, and new tick species are being introduced including Haemaphysalis longicornis (the Asian longhorned tick), an invasive species which is a vector for several human infections. While many state- and local-level jurisdictions have tick surveillance programs, these by necessity cover large geographic areas leading to increased expense and inefficiency. As a consequence, fundamental aspects of the epidemiology of tick-borne diseases remain obscure; and no methods currently exist to identify and target physical locations with highest risk for tick-borne disease transmission. Therefore, the studies proposed here are directed to understanding key aspects of the connections between human outdoor activities and tick populations to develop more targeted health surveillance programs. First, we will enroll both persons with confirmed tick- borne disease and those without, and we will assess risk factors for infection. We will then capture and compare human mobility patterns in both groups using geographic position system (GPS) data loggers; these data will be used to identify locations of significant risk. Secondly, we will perform comprehensive tick surveys at all locations with either high or low risk, and will compare tick abundance and pathogen prevalence between sites to confirm results from the spatial analysis. Our findings will dramatically expand our ability to directly and efficiently target surveillance and interventions to address a critically important public health problem.